The development of head and neck cancer may depend upon an interaction between both environmental carcinogens and a genetic susceptibility to those carcinogens. The need to understand such interaction in the head and neck cancer population is heightened by their associated risk for the development of second primary neoplasias, such as lung and digestive tract cancers. With an improved understanding, the relative risk of second malignancies can be more precisely defined. Preventive therapy could then be more appropriately targeted. The head and neck cancer population thus represents a potential target population for prevention of multiple diverse environmentally-induced cancers. This proposal is comprised of a series of objectives in which the primary goal is to establish a quantitative risk assessment model for second primary malignancies in head and neck cancer patients. We will demonstrate that the addition of quantitative measures of mutagen-sensitivity expressed by a respective patient will significantly improve that model. The relationship of total carcinogen exposure (namely to tobacco and alcohol) both before and after treatment to the development of second primary malignancies will be established. Mutagen-sensitivity will be determined by culturing lymphocytes from each patient, arresting lymphocytes in metaphase, exposing them to the clastogen bleomycin, and assessing for bleomycin-induced chromatid breaks in cytogenetic preparations. Results from this study will form a basis for determining the potential biologic significance of chromosomal sensitivity in cancer development. Results will, likewise, provide insight into future stratification considerations for therapeutic intervention trials involving prevention of second malignancies in the head and beck cancer population.